Cells of a cloned line of murine virusinduced erythroleukemia were stimulated to differentiate along the erythroid pathway by dimethyl sulfoxide at concentrations that did not inhibit growth. A rise in the number of benzidine-positive normoblasts was accompanied by increased synthesis of heme and hemoglobin and a decrease in the malignancy of the cells. This action of dimethyl sulfoxide, which was reversible, may represent the derepression of leukemic cells to permit their maturation.The opportunity to explore the possibility that leukemia is a disease resulting from a block in the process of maturation of hematopoietic cells has been provided by established tissue culture lines of murine virus-induced erythroleukemic cells (1-3). These cells, which grow in suspension, have continued to exhibit a limited degree of differentiation along the erythroid line throughout their 4-year serial passage history. Although they synthesize hemoglobin (4, 5), they are malignant as tested by bioassay in syngeneic hosts. They produce virus which, although low in leukemogenic activity, is a highly effective immunizing agent (6).During the course of studies to determine the effect of superinfecting these cells with Friend leukemia virus, dimethyl sulfoxide (DMS0) was added to the medium. DMS0 had been demonstrated to enhance infectivity of both poliovirus RNA (7) and mengovirus RNA (8), as well as transformation by polyoma virus (9). It is also known to stabilize enveloped viruses (10). The wide range of biological activities of DMSO has been described (11). The present report de-scribes an effect of DMSO on the differentiation of established lines of murine virus-induced leukemic cells and illustrates still another property of this compound.In the dose-response experiments initially set up to determine the toxicity of DMSO on the leukemic cell lines, a striking effect on the differentiation of these cells was noted. Of the cells allowed to grow in medium containing 2% DMS0 for 4 days, a majority of the erythroblasts had matured to normoblasts which stained benzidine-positive (B+). The increase in the number of cells maturing along the erythroid series in DMS0-containing medium was accompanied by an increase in the amount of hemoglobin synthesized. MATERIALS AND METHODSThe origin of the cell lines of murine Friend leukemia virusinduced leukemic cells and their clonal derivatives has been described previously (1,2). Methods for maintaining the cell culture, cloning on semisoft agar, and the medium were also detailed in these earlier reports.The present experiments were done on a clone designated 707, in which 1-2% of the cells are B+ (5). Cells were generally seeded at a concentration of 105 per ml (except where otherwise indicated) either in 32-oz. (900 ml) prescription bottles containing 60 ml of medium or in Falcon plastic Petri dishes (60 X 15 mm) containing 10 ml of medium. Dehydrated Eagle's basal medium diluted with Earle's balanced salt solution and supplemented with 15% fetal calf serum was used. The cultures were ...
A disease with the characteristics of a leukemia has been found to be serially transmissible in adult Swiss mice by means of cell-free filtrates. Thus far, the disease has been transmitted through twenty-six serial passages with filtrates as well as cell suspensions. The agent readily passes through Selas 03, Berkefeld N, and gradocol membrane filters—these last having an average pore size of 220 mµ. Filtrates remain stable when stored for long periods at –70°C. or when lyophilized. Splenic tissue containing the agent, which was subjected to massive doses of x-ray (50,000 r),—far more than sufficient to kill the cells,—show undiminished infectivity. The agent is inactivated by heating to 56°C. for 30 minutes and by exposure to ether or formalin. The disease can be transmitted to adult Swiss mice or DBA/2 mice, but not to adult PRI, C3H, A, C57B1/6, or F1(C58 x BALB) mice. Intraperitoneal, subcutaneous, intracerebral, and intramuscular injections are all effective.
BackgroundProstate cancer is the most common cancer in men in the UK. NICE guidelines on recognition and referral of suspected cancer, recommend performing digital rectal examination (DRE) on patients with urinary symptoms and urgently referring if the prostate feels malignant. However, this is based on the results of one case control study, so it is not known if DRE performed in primary care is an accurate method of detecting prostate cancer.MethodsThe aim of this review is to ascertain the sensitivity, specificity, positive and negative predictive value of DRE for the detection of prostate cancer in symptomatic patients in primary care.CENTRAL, MEDLINE, EMBASE and CINAHL databases were searched in august 2015 for studies in which a DRE was performed in primary care on symptomatic patients and compared against a reference diagnostic procedure.ResultsFour studies were included with a total of 3225 patients. The sensitivity and specificity for DRE as a predictor of prostate cancer in symptomatic patients was 28.6 and 90.7%, respectively. The positive and negative predictive values were 42.3 and 84.2%, respectively.ConclusionThis review found that DRE performed in general practice is accurate, and supports the UK NICE guidelines that patients with a malignant prostate on examination are referred urgently for suspected prostate cancer. Abnormal DRE carried a 42.3% chance of malignancy, above the 3% risk threshold which NICE guidance suggests warrants an urgent referral. However this review questions the benefit of performing a DRE in primary care in the first instance, suggesting that a patient’s risk of prostate cancer based on symptoms alone would warrant urgent referral even if the DRE feels normal.
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